P
US7687628B2ExpiredUtilityPatentIndex 95

Method of preparing 4-amino-1H-imidazo(4,5-c)quinolines and acid addition salts thereof

Assignee: TARO PHARMACEUTICALS USA INCPriority: Oct 1, 2003Filed: Sep 30, 2004Granted: Mar 30, 2010
Est. expiryOct 1, 2023(expired)· nominal 20-yr term from priority
Inventors:GUTMAN DANIELLABAIDOSSI WAELCHERNYAK SHIMON
C07D 401/04
95
PatentIndex Score
56
Cited by
42
References
20
Claims

Abstract

The present invention provides a method of preparing a 4-(arylmethyl)amino-1H-imidazo(4,5-c)quinoline of formula (4) by reacting an arylmethylamine of formula (3) with a 4-chloro-1H-imidazo(4,5-c)quinoline of formula (2). The present invention further provides a method of preparing an acid addition salt of formula (5) comprising the step of hydrolyzing a 4-(arylmethyl)amino-1H-imidazo(4,5-c)quinoline of formula (4) with a strong acid, HX. The present invention further provides a method of preparing a 4-amino-1H-imidazo(4,5-c)quinoline of formula (1) comprising the step of treating an acid addition salt of formula (5) with a base.

Claims

exact text as granted — not AI-modified
1. A method of preparing an acid addition salt of formula (5) 
       
         
           
           
               
               
           
         
       
       consisting of the step of hydrolyzing a 4-(arylmethyl)amino-1H-imidazo(4,5-c)quinoline of formula (4) with a strong acid, HX, 
       
         
           
           
               
               
           
         
       
       wherein
 R 1  and R 2  are independently selected from the group consisting of hydrogen, C 1 -C 4  alkyl, C 3 -C 4  cycloalkyl, C 2 -C 4  alkenyl, and C 2 -C 4  alkynyl, 
 each of R 5 , R 6 , R 7 , R 8 , and R 9  is hydrogen, and 
 X −  is a conjugate base of a strong acid, 
 
       thereby forming an acid addition salt of formula (5), 
       wherein at least one of R 1  and R 2  is hydrogen. 
     
     
       2. The method of  claim 1 , wherein the 4-(arylmethyl)amino-1H-imidazo(4,5-c)quinoline of formula (4) is prepared by reacting benzylamine with a 4-chloro-1H-imidazo(4,5-c)quinoline of formula (2) 
       
         
           
           
               
               
           
         
       
     
     
       3. The method of  claim 1 , wherein the strong acid is selected from the group consisting of sulfuric acid, methanesulfonic acid, trifluoromethanesulfonic acid, and mixtures thereof. 
     
     
       4. The method of  claim 1 , further comprising treating the acid addition salt of formula (5) with a base to provide a 4-amino-1H-imidazo(4,5-c)quinoline of formula (1) 
       
         
           
           
               
               
           
         
       
     
     
       5. The method of  claim 4 , wherein the base is selected from the group consisting of sodium hydroxide, potassium hydroxide, and mixtures thereof. 
     
     
       6. The method of  claim 4 , wherein the 4-amino-1H-imidazo(4,5-c)quinoline of formula (1) is 4-amino-1-isobutyl-1H-imidazo[4,5-c]quinoline. 
     
     
       7. The method of  claim 1 , wherein the hydrolyzing step is performed for less than about four hours. 
     
     
       8. The method of  claim 1 , wherein the hydrolyzing step is performed for less than about two hours. 
     
     
       9. The method of  claim 1 , wherein the hydrolyzing step provides the acid addition salt of formula (5) at a yield of at least about 70%. 
     
     
       10. The method of  claim 1 , wherein the hydrolyzing step provides the acid addition salt of formula (5) at a yield of at least about 80%. 
     
     
       11. The method of  claim 2 , wherein the 4-(arylmethyl)amino-1H-imidazo(4,5-c)quinoline of formula (4) is prepared in a neat reaction. 
     
     
       12. The method of  claim 2 , wherein the 4-(arylmethyl)amino-1H-imidazo(4,5-c)quinoline of formula (4) is prepared at a temperature of about 100° C. to about 140° C. 
     
     
       13. The method of  claim 1 , wherein R 1  and R 2  are independently selected from the group consisting of hydrogen and C 1 -C 4  alkyl. 
     
     
       14. The method of  claim 13 , wherein the 4-(arylmethyl)amino-1H-imidazo(4,5-c)quinoline of formula (4) is prepared by reacting benzylamine with a 4-chloro-1H-imidazo(4,5-c)quinoline of formula (2) 
       
         
           
           
               
               
           
         
       
     
     
       15. The method of  claim 1 , comprising preparing an acid addition salt of formula (25) 
       
         
           
           
               
               
           
         
       
       consisting of hydrolyzing 4-(N-benzylamino)-1-isobutyl-1H-imidazo(4,5-c)quinoline (formula (24)) with the strong acid, HX, 
       
         
           
           
               
               
           
         
       
       thereby forming the acid addition salt of formula (25). 
     
     
       16. The method of  claim 15 , wherein the 4-(N-benzylamino)-1-isobutyl-1H-imidazo(4,5-c)quinoline (formula (24)) is prepared by reacting benzylamine with 4-chloro-1-isobutyl-1H-imidazo(4,5-c)quinoline (formula (22)) 
       
         
           
           
               
               
           
         
       
     
     
       17. The method of  claim 1 , wherein R 1  is hydrogen and R 2  is isobutyl. 
     
     
       18. The method of  claim 17 , wherein the 4-(arylmethyl)amino-1H-imidazo(4,5-c)quinoline of formula (4) is prepared by reacting benzylamine with a 4-chloro-1H-imidazo(4,5-c)quinoline of formula (2) 
       
         
           
           
               
               
           
         
       
     
     
       19. The method of  claim 1 , wherein the strong acid is sulfuric acid. 
     
     
       20. A method of preparing an acid addition salt of formula (5) 
       
         
           
           
               
               
           
         
       
       consisting essentially of the step of hydrolyzing a 4-(arylmethyl)amino-1H-imidazo(4,5-c)quinoline of formula (4) with a strong acid, HX, 
       
         
           
           
               
               
           
         
       
       wherein
 R 1  and R 2  are independently selected from the group consisting of hydrogen, C 1 -C 4  alkyl, C 3 -C 4  cycloalkyl, C 2 -C 4  alkenyl, and C 2 -C 4  alkynyl, 
 each of R 5 , R 6 , R 7 , R 8 , and R 9  is hydrogen, and 
 X −  is a conjugate base of a strong acid, 
 
       thereby forming an acid addition salt of formula (5), 
       wherein at least one of R1 and R2 is hydrogen.

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